Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development.

Autor:	Courreges CJF; Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom.; Department of Pathology, The University of Cambridge, Cambridge, United Kingdom., Davenport ECM; Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom.; Royal Veterinary College, London, United Kingdom., Bilanges B; UCL Cancer Institute, University College London, London, United Kingdom., Rebollo-Gomez E; UCL Cancer Institute, University College London, London, United Kingdom., Hukelmann J; The School of Life Sciences, University of Dundee, Dundee, United Kingdom., Schoenfelder P; Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom., Edgar JR; Department of Pathology, The University of Cambridge, Cambridge, United Kingdom., Sansom D; Institute of Immunity and Transplantation, University College London, London, United Kingdom., Scudamore CL; Royal Veterinary College, London, United Kingdom., Roychoudhuri R; Department of Pathology, The University of Cambridge, Cambridge, United Kingdom., Garden OA; Royal Veterinary College, London, United Kingdom., Vanhaesebroeck B; UCL Cancer Institute, University College London, London, United Kingdom., Okkenhaug K; Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom.; Department of Pathology, The University of Cambridge, Cambridge, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Nov 27; Vol. 15, pp. 1374621. Date of Electronic Publication: 2024 Nov 27 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1374621
Abstrakt:	Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cells in vitro . Our data suggest that VPS34 is required for the maintaining normal numbers of mature Treg. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy may contribute to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells. Competing Interests: BV and KO are consultants for iOnctura Geneva, Switzerland. KO is a consultant for Macomics Edinburgh, UK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Courreges, Davenport, Bilanges, Rebollo-Gomez, Hukelmann, Schoenfelder, Edgar, Sansom, Scudamore, Roychoudhuri, Garden, Vanhaesebroeck and Okkenhaug.)
Databáze:	MEDLINE
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